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P. quassioides is a traditional Chinese medicine used for the treatment of gastroenteritis, snakebite, infection and hypertension in China. 4, 5-dimethoxycanthin-6-one is one of the main active canthinone alkaloid isolated from P. quassioides. The aim of this work was to identify the cytochrome P (CYP) 450 enzymes responsible for the metabolism of 4, 5-dimethoxycanthin-6-one (DCO) and to evaluate the inhibitory effect of DCO on CYP activity in human liver microsomes (HLM) in vitro.the CYP isoforms responsible for DCO metabolism and the inhibitory effects of DCO on CYP activity was studied in HLM.The in vitro metabolic enzyme of DCO was CYP3A4 (mediated the formation of metabolites M1-M5), CYP2C9 (mediated the formation of metabolites M1-M3, M6 and M8) and CYP2D6 (mediated the formation of metabolite M3) in HLM. Furthermore, the present work found that DCO uncompetitively inhibited CYP1A2-mediated phenacetin O-deethylation with an IC50 value of 1.7 μM and a Ki value of 2.6 μM.The results suggested that the metabolic interaction should be existed when the substrate drugs of CYP1A2 were co-administered with DCO or traditional Chinese medicine containing it, such as the extract of P. quassioides and Kumu injection.